Cell Biology and Intracellular Gene Delivery
Key staff: Dr Simon Richardson
With Dr Richardson trained formally as a drug delivery scientist as well as in molecular cellular biology, the Richardson Laboratory is uniquely placed to work at the interface of these two disciplines. Our principal interest is in delivering macromolecular drugs such as genes, oligonucleotides and proteins to the cytosol of the cell by exploiting retrograde transport steps. Retrograde transport is responsible for the recycling of membrane components after the fusion of intracellular vesicles, which move material to different parts of the cell. As the proteins responsible for this movement are immunogenic, soluble polymer drug-delivery systems are being evaluated as agents that can be conjugated to the intracellular delivery. This is in order to mask the intracellular drug-delivery protein from the immune system while it is in transit to the target cell type. This research is being performed in collaboration with Dr Nathalie Lavignac, a faculty member of the Medway School of Pharmacy.
It is expected that this technology will be able to deliver anti-cancer agents such as the protein p53 to the cytosol of p53-deficient cancer cells – a reactivation event that has been reported to cause complete tumour regression (Cell (2007) 128, 837).
Furthermore, we envisage that this technology may be used to develop a new generation of safe and efficient anti-viral agents, delivering either antibody FAb fragments, RNAi oligonucleotides or dominant negative proteins that can arrest the viral life cycle.
In addition to membership of the Controlled Release Society, the American Society for Cell Biology and the Institute of Biology, Dr Richardson is also a member of the Engineering and Physical Sciences Research Council (EPSRC)’s Nanomedicine platform, based at Cardiff University. Please see www.gre.ac.uk/nanomedicine for more details.
Publications
Chu, Y. et al. (2006). Endocytosis of extracellular superoxide dismutase into endothelial cells: role of heparin-binding domain. Arterioscler. Thromb. Vasc. Biol. 26 (9), 1985–1990.
Pryor, P. R. et al. (2004). Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO Reports. 5 (6), 1–6.
Richardson, S. C. W. et al. (2004). Mammalian late Vps orthologues participate in early endosomal fusion and interact with the cytoskeleton. Mol. Biol. Cell, 15, 1197–1210.
Richardson, S. C. W. et al. (2008). The use of fluorescence microscopy to define polymer conjugate localisation to late endocytic compartments in fixed and live target cells. Journal of Controlled Release 127, 1–11.
Zhang, Y. et al. (2007). A defect in the signaling lipid phosphatidylinositol 3,5-bisphosphate causes neurodegeneration in Mice. Proc. Nat. Acad. Sci. USA, 104 (44), 17518–17523.